The present invention relates to a multi-step process for hydroxylating 4-substituted biphenyls to make 4'-substituted-3-hydroxy-biphenyls involving a biological step and chemical steps. More particularly, the present invention relates to the employment of certain mutant strains of Alcaligenes eutrophus NRRLB-15940 or Pseudomonas putida NRRLB-18064, which perform the biological conversion of 4-substituted biphenyls to the corresponding optically active (1S-cis)-3-(4-substituted phenyl)-3,5-cyclohexadiene-1,2-diols. The acylation of such intermediate and cleavage of the 2-acyloxy group and the 3-proton with bases from the resulting (1S-cis)-3-(4-substituted phenyl)-3,5-cyclohexadiene-1,2-diacylate followed by its hydrolysis, results in the production of the 4'-substituted-3-hydroxybiphenyl.
Prior to the present invention, 4'-substituted-3-hydroxybiphenyls of the formula, ##STR1## where Y is a member selected from the class consisting of nitro, halo, carboxy and hydroxy and preferably hydroxy, required multi-step chemical procedures which resulted in a low overall yield. Enzymatic hydroxylation of biphenyl and certain 4-substituted biphenyls using whole cells is shown by
Ziffer et al., Tetrahedron, 33, 2491 (1977) and Taylor, European Patent Application EP No. 76606A1, Apr. 13, 1983. Masse et al. also refers to the enzymatic treatment of 4-chlorobiphenyl in Applied Environmental Microbiology, 47, 947 (1984). Although various chemical and biological procedures have been used to modify 4-substituted biphenyls, satisfactory techniques for making 4'-substituted 3-hydroxybiphenyls of formula (1), particularly where Y is hydroxy, are constantly being sought.